Danger: Alzheimer's disease Progression Is Linked to Olfactory Viral Inflammation

Viruses can inflame and damage connections between the olfactory system and the area of the brain related to memory and learning, potentially hastening the onset of Alzheimer's disease, according to a recent study. The olfactory system is the sensory system that allows humans to smell.

Olfactory viral inflammation refers to the inflammation of the olfactory (sense of smell) system due to a viral infection. The olfactory system includes the olfactory neurons (nerve cells that detect odors) in the nose, as well as the olfactory bulb (a part of the brain that processes smell information).

Viral infections that can cause olfactory viral inflammation include the common cold, influenza (the flu), and the respiratory syncytial virus (RSV). These infections can lead to inflammation of the mucous membranes lining the inside of the nose, which can damage the olfactory neurons and impair the sense of smell.

Symptoms of olfactory viral inflammation may include a reduced sense of smell or a complete loss of smell (anosmia), as well as other cold or flu-like symptoms such as congestion, coughing, and sneezing. In most cases, the sense of smell will return to normal once the viral infection has resolved. In some cases, however, the damage to the olfactory neurons may be permanent, leading to a long-term loss of smell.

Researchers at CU Anschutz believe it disturbs the olfactory tract, affecting the hippocampus, which governs memory and learning.

According to a new study from researchers at the University of Colorado Anschutz Medical Campus, viruses can inflame and disrupt connections between the olfactory system, which governs the sense of smell, and the part of the brain associated with memory and learning, potentially accelerating the onset of Alzheimer's disease.

The results, published on December 13 in the journal Neurobiology of Aging, might lead to novel medicines that identify Alzheimer's disease (AD) early while also shedding light on the role that viruses and the olfactory system play in causing the disease.

"We know that losing one's sense of smell is one of the early indications of Alzheimer's disease," said study main author Andrew Bubak, Ph.D., assistant research professor in the division of neurology at the University Of Colorado School Of Medicine”.

Bubak's team concentrated on the olfactory bulb, olfactory tract, and the hippocampus, the part of the brain responsible for memory and learning.

They looked at messenger RNA in the brain tissue of six Colombians with Familial Alzheimer's disease (FAD) and tissue from a control group that didn't have AD. They discovered signs of viral infection in the FAD group's olfactory bulbs, as well as inflammation in the olfactory tract, which transports information to the hippocampus. In addition, they detected abnormal myelination in the olfactory tract. Myelin is a fatty layer that surrounds neurons and permits electrical impulses to flow fast and smoothly. Signaling is halted if it is damaged.

"These findings suggest the hypothesis that viral infection, accompanying inflammation, and dysregulation of olfactory system myelination may alter hippocampus function, leading to the acceleration of FAD development," according to the study.

Viruses have long been suspected of playing a role in cognition disorders, according to the study's senior authors, Maria Nagel, MD, research professor in neurology, and Diego Restrepo, PhD, professor of cell and developmental biology at the CU School of Medicine. Some research has linked the SARS-CoV-2 virus, which produces COVID-19, to dementia. The virus, which spreads through the nose, causes some afflicted people to lose their sense of smell.

Simultaneously, the varicella zoster virus, which causes shingles, and the herpes simplex virus can deposit amyloid beta, a protein required for the development of Alzheimer's disease, in the olfactory bulb. Even after symptoms have subsided, viruses can live on for years.

"Our idea is that some viruses accelerate the progression of Alzheimer's disease," Restrepo explained. "Does the loss of smell especially aggravate Alzheimer's disease? That is the query."

Bubak and Restrepo believe that inflammation and amyloid deposits in the olfactory system are interfering with communication with the hippocampus. They think that without sensory information, the hippocampus begins to atrophy.

"The whole olfactory pathway leads to the hippocampus.”If you reduce signaling along that route, you get less signaling to the hippocampus," explained Bubak. "You lose it if you don't use it."

The next step for the researchers is to better understand the interaction between the olfactory system and the hippocampus in the setting of viral susceptibility and neurodegeneration.

There is evidence to suggest that certain viral infections may increase the risk of neurodegeneration, which is the loss of function or death of nerve cells in the brain and other parts of the nervous system. Some studies have found that viral infections may contribute to the development of neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. For example, research has suggested that the herpes simplex virus type 1 (HSV-1), which is a common cause of cold sores, may be a risk factor for Alzheimer's disease.

There is also evidence to suggest that people with neurodegenerative disorders may be more susceptible to viral infections. For example, people with Parkinson's disease may have a weaker immune system and may be more prone to respiratory infections. Additionally, some medications used to treat neurodegenerative disorders may weaken the immune system, which may also increase the risk of viral infections.

There is evidence to suggest that certain viral infections may increase the risk of neurodegeneration, which is the loss of function or death of nerve cells in the brain and other parts of the nervous system. Some studies have found that viral infections may contribute to the development of neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease.

For example, research has suggested that the herpes simplex virus type 1 (HSV-1), which is a common cause of cold sores, may be a risk factor for Alzheimer's disease. Other viruses that have been linked to neurodegeneration include the human immunodeficiency virus (HIV), which can cause HIV-associated neurocognitive disorders (HAND), and the Epstein-Barr virus (EBV), which has been associated with multiple sclerosis (MS).

It is important to note that the relationship between viral infections and neurodegeneration is complex and more research is needed to fully understand the potential link between these conditions. Additionally, it is worth noting that while some viral infections may increase the risk of neurodegeneration, others may have protective effects against neurodegenerative disorders.

Reference: Bubak, A. N., Merle, L., Niemeyer, C. S., Dnate’Baxter, B., Polese, A. G., Ramakrishnan, V., ... & Restrepo, D. (2022). Signatures for Viral Infection and Inflammation in the Proximal Olfactory System in Familial Alzheimer's Disease. Neurobiology of Aging. DOI: 10.1016/j.neurobiolaging.2022.12.004